This Program Project proposal is directed toward the solution of several of the principal obstacles which persist in the field of heart transplantation. Improved control of the rejection response will be sought by the use of monoclonal antibody reagents against the various subsets of human T lymphocytes, both to evaluate the alterations in these cells which occur with transplantation and immunosuppression and to produce desired effects on these cell populations by employing these same hybridoma-produced agents in treatment. Initial trials will employ kidney transplant patients. Newer approaches to the use of these agents will be evaluated in primates against whose cells of the anti-human reagents are effective. Other studies will include the assessment of recipient immunity by new methods against donor cells other than lymphoid cells, especially endothelium, an effort to reduce or eliminate states of pre-existing immunity in patients to prospective donors by prolonged courses of treatment with antibodies against T cells, a new approach to transplant evaluation in which radioactively labeled antibodies to cardiac myosin components can be visualized by external imaging in the damaged myocardium of transplants, an exploration of the importance of cytomegalovirus infections in the outcome of transplant procedures, and consideration of the immunogenetics of xenograft survival in certain species.